DESCRIPTION (Verbatim from the applicant's abstract): The long term goal of this research is to understand the role of histone acetylation and deacetylation in chromatin structure and function, using the yeast Saccharomyces cerevisiae to study these processes. Since many of the yeast proteins involved in acetylation/deacetylation have human homologs, this project should shed light on human biology and disease. The specific aims for this period are: 1) to learn about the enzymatic mechanism of Sir2 and related proteins, recently demonstrated to be NAD-dependent protein deacetylases, 2) to determine if the role of Sir2 in transcriptional silencing is histone deacetylation, 3) to determine the in vivo roles of the yeast Sir2 homologs Hst2, Hst3 and Hst4, 4) to understand how the proteins SUM1-1 and Hstl can silence the mating type loci, HML and HMR, in the absence of Sir2, and 5) to demonstrate that the yeast proteins Sas2 and SptlO are acetyltransferases and to determine if their substrates are histones or other proteins,